tbuckley/cabot-search huggingface dataset:
In-organoid single-cell CRISPR screening reveals determinants of hepatocyte differentiation and maturation
Authors: Junbo Liang, Jinsong Wei, Jun Cao, Jun Qian, Ran Gao, Xiaoyu Li, Dingding Wang, Yani Gu, Lei Dong, Jia Yu, Bing Zhao, Xiaoyue Wang
Journal: Genome biology (2023)

Harnessing hepatocytes for basic research and regenerative medicine demands a complete understanding of the genetic determinants underlying hepatocyte differentiation and maturation. Single-cell CRISPR screens in organoids could link genetic perturbations with parallel transcriptomic readout in single cells, providing a powerful method to delineate roles of cell fate regulators. However, a big challenge for identifying key regulators during data analysis is the low expression levels of transcription factors (TFs), which are difficult to accurately estimate due to noise and dropouts in single-cell sequencing. Also, it is often the changes in TF activities in the transcriptional cascade rather than the expression levels of TFs that are relevant to the cell fate transition.Here, we develop Organoid-based Single-cell CRISPR screening Analyzed with Regulons (OSCAR), a framework using regulon activities as readouts to dissect gene knockout effects in organoids. In adult-stem-cell-derived liver organoids, we map transcriptomes in 80,576 cells upon 246 perturbations associated with transcriptional regulation of hepatocyte formation. Using OSCAR, we identify known and novel positive and negative regulators, among which Fos and Ubr5 are the top-ranked ones. Further single-gene loss-of-function assays demonstrate that Fos depletion in mouse and human liver organoids promote hepatocyte differentiation by specific upregulation of liver metabolic genes and pathways, and conditional knockout of Ubr5 in mouse liver delays hepatocyte maturation.Altogether, we provide a framework to explore lineage specifiers in a rapid and systematic manner, and identify hepatocyte determinators with potential clinical applications.
OA04.04 The Registry of Genetic Alterations of Taiwan NSCLC by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study - TCOG T1521 Study
Authors: B.-C. Liao, N.-J. Chiang, G.-C. Chang, W.-C. Su, I.-W. Chong, T.-Y. Yang, Y.-H. Luo, C.-L. Lai, T.-C. Hsia, C.-L. Ho, K.-Y. Lee, C.-F. Hsiao, J.C.-H. Yang
Journal: Journal of Thoracic Oncology (2023)
EP06.05-04 SMARCA4/BRG1 Deficient Thoracic Neoplasms: Spectrum Encompassing Carcinomas to Undifferentiated Tumors
Authors: A. Tandon, A. Nambirajan, S. Chandrashekhara, A. Mohan, S. Kumar, P.S. Malik, D. Jain
Journal: Journal of Thoracic Oncology (2023)
MA05.11 Predictive Utility of Patient-Reported Outcomes for Survival in 1st-Line Treated Patients with a NSCLC in EMPOWER-Lung 1 and 3
Authors: D.R. Gandara, M. Gogishvili, A. Sezer, T. Makharadze, M. Gümüş, D.A. McIntyre, X. He, E. Yan, G. Gullo, P. Rietschel, R.G. Quek
Journal: Journal of Thoracic Oncology (2023)
MA16.04 Circulating Tumor DNA Quantification by NGS Should Be Adapted to the Methodology Used
Authors: R. Serna Blasco, E. Nadal, V. Calvo, J.L. Gonzalez-Larriba, A. Insa, B. Massutí, M.R. Garcia-Campelo, A. Martinez-Marti, J. Casal, A. Garrido Fernandez, J. Bosch-Barrera, M. Dómine, J. De Castro, S. Ponce, M. Majem, D. Rodriguez-Abreu, N. Reguart, R. Bernabé, I. Barneto, M. Cobo, C. Camps, G. López Vivanco, E. Del Barco, A. Aguilar, T. Moran, R. Lopez-Castro, A. Cruz-Bermúdez, A. Romero, M. Provencio
Journal: Journal of Thoracic Oncology (2023)
MA14.10 Spatiotemporal Heterogeneity of Genomic and Transcriptomic Landscape of Multiple Lung Cancer by a Novel Multi-omics Algorithm
Authors: Y. Song, J. Hu, J. Zhou, D. Zhang, Y. Zhang, X. Xu, J. Pang, H. Bao, J.C. Yin, Y. Shao
Journal: Journal of Thoracic Oncology (2023)
MA14.08 Pathogenic Germline Variants in Patients with Non-Small Cell Lung Cancer (NSCLC) Detected by Tissue Comprehensive Genomic Profiling
Authors: L. Mezquita, Z. Kuang, S. Sivakumar, E.S. Sokol, J.C. Laguna, B. Pastor, I. Nalda, F. Turrisi, L. Aguilar, A. Arcocha, M. Potrony, X. Solé, C. Teixido, A. Prat, B. Besse
Journal: Journal of Thoracic Oncology (2023)
MA08.11 Initial Chemotherapy for Locally Advanced and Metastatic NUT Carcinoma
Authors: J. Luo, B. Finstein, M. Sanchez, E. Lee, H. Hertzler, N. Luong, R. Tamen, G. Brisbane, T. Nguyen, P.K. Paik, J.E. Chaft, S. Piha-Paul, P.A. Jänne, L.M. Sholl, M. Cheng, S.G. DuBois, G.J. Hanna, M. Nishino, G.I. Shapiro, C.A. French
Journal: Journal of Thoracic Oncology (2023)
OA09.05 A Phase 3 Study of Serplulimab Plus Chemotherapy as First-Line Treatment for Squamous Non-small-Cell Lung Cancer (ASTRUM-004)
Authors: C. Zhou, Y. Hu, E. Arkania, S. Kilickap, K. Ying, F. Xu, L. Wu, X. Wang, M. Viguro, T. Makharadze, H. Sun, F. Luo, J. Shi, A. Zang, Y. Pan, Z. Chen, Z. Jia, V. Kuchava, P. Lu, L. Zhang, Y. Cheng, W. Li, W. Kang, Q. Wang, G. Yang, H. Yu, J. Li, J. Zhu
Journal: Journal of Thoracic Oncology (2023)
Combining clinical notes with structured electronic health records enhances the prediction of mental health crises
Authors: Roger Garriga, Teodora Sandra Buda, João Guerreiro, Jesús Omaña Iglesias, Iñaki Estella Aguerri, Aleksandar Matić
Journal: Cell Reports Medicine (2023)

An automatic prediction of mental health crises can improve caseload prioritization and enable preventative interventions, improving patient outcomes and reducing costs. We combine structured electronic health records (EHRs) with clinical notes from 59,750 de-identified patients to predict the risk of mental health crisis relapse within the next 28 days. The results suggest that an ensemble machine learning model that relies on structured EHRs and clinical notes when available, and relying solely on structured data when the notes are unavailable, offers superior performance over models trained with either of the two data streams alone. Furthermore, the study provides key takeaways related to the required amount of clinical notes to add value in predictive analytics. This study sheds light on the untapped potential of clinical notes in the prediction of mental health crises and highlights the importance of choosing an appropriate machine learning method to combine structured and unstructured EHRs.
OA22.04 BRIGHTSTAR Local Consolidative Therapy with Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC
Authors: Y. Elamin, S. Gandhi, M. Saad, S. Rehmani, M.B. Antonoff, D.L. Gibbons, X. Le, M. Negrao, V. Lam, M. Altan, J. Tu, C. Gay, L. Byers, T. Cascone, G. Blumenschein, J. Chang, A. Vaporciyan, Z. Liao, S. Swisher, J. Yin, K. Park, P. Zhang, J. Wu, J. Heymach
Journal: Journal of Thoracic Oncology (2023)
EP13.06-06 Exploratory Clinical Study of Anlotinib Combined with Concurrent Chemoradiotherapy in the Treatment of Small Cell Lung Cancer(SCLC)
Authors: F. Yang, M. Xing, R. Li, H. Zhao, L. Ren, M. Zhang, J. Xu, L. Wang, M. Wang, H. Xu, F. Zhang
Journal: Journal of Thoracic Oncology (2023)
EP14.02-03 Open Versus Video-Assisted and Robotic-Assisted Thymectomy for the Treatment of Thymic Neoplasms
Authors: B. Huo, Y. Lee, K-M. Kontouli, P. Patel, K. Yang, A. Jong, K. Coyle, D.G. French, A. Wallace, M. Plourde
Journal: Journal of Thoracic Oncology (2023)
EP17.03-04 The Economic Evaluation of The protein-Based Lung Cancer Biomarker Panel (LCBP):Evidencebased Onamulticenter Clinicaltrialin China
Authors: D. Yang, A. Adilan, Y. Zhang, J. Hu, H. Qun, H. Weng, Y. Song, J. Zhou, P. Charels, J. Xuan, C. Bai
Journal: Journal of Thoracic Oncology (2023)
EP06.03-21 Usefulness of Immunohistochemistry for the Detection of BRAFV600E in Lung Cancer: A Multicenter Retrospective Study in China
Authors: P. Yuan, L. Wang, X. Gao, J. Hou, R. Huang, M. Qi, C. Guo, X. Xue, J. Ying
Journal: Journal of Thoracic Oncology (2023)
OA21.06 ctDNA Dynamics, Prognostic Markers and Resistance Mechanisms in Tepotinib-Treated METex14 Skipping NSCLC in the VISION Trial
Authors: X. Le, M.C. Garassino, M.-J. Ahn, E. Felip, A.B. Cortot, H. Sakai, J. Mazieres, M. Thomas, S. Viteri, P. Conte, J.C.-H. Yang, W.T. Iams, F. Griesinger, C. Stroh, D. Juraeva, D. Wang, A. Johne, P.K. Paik
Journal: Journal of Thoracic Oncology (2023)
OA13.04 Profile of Reactive Estrogen Species in Women with EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)
Authors: J.N. Bodor, D.D. Krzizike, L. Vanderveer, S. Eidbo, C.L. Zawislak, E.A. Ross, A.J. Andrews, M.J. Edelman, J. Treat, M.L. Clapper
Journal: Journal of Thoracic Oncology (2023)
MA19.09 AI-Based Early Detection and Subtyping of Non-Small Cell Lung Cancer from Blood Samples Using Orphan Noncoding RNAs
Authors: M. Karimzadeh, T.B. Cavazos, J. Wang, M. Multhaup, Y. Fang, J. Ku, J. Wang, X. Zhao, K. Wang, R. Hanna, O.I. Afolabi, A. Huang, D. Corti, K. Garcia, T. Joshi, D. Nguyen, Y. Kong, P. Arensdorf, K.H. Chau, A. Hartwig, H. Li, S. Patel, H. Goodarzi, L. Fish, F. Hormozdiari, B. Alipanahi
Journal: Journal of Thoracic Oncology (2023)
EP14.03-01 Is Subxiphoid Uniportal Video-Assisted Thoracoscopic Mediastinal Surgery Safe, Minimally Invasive, and Radical?
Authors: Y. Mori, Y. Sano, S. Otani, N. Sakao, Y. Kiriyama, T. Sugihara, T. Ishimura, T. Ueki, F. Ogura
Journal: Journal of Thoracic Oncology (2023)
OA06.05 Consensual Definition of Stage III NSCLC Resectability: EORTC-Lung Cancer Group Initiative with Other Scientific Societies
Authors: A.-M. Dingemans, J. Remon, L. Hendriks, J. Edwards, C. Faivre-Finn, N. Reguart, E. Smit, A. Levy, D. Sanchez, J.C. Trujillo, A. Filippi, K. Stathopoulos, T.G. Blum, M. Guckenberger, S. Popat, I. Opitz, A. Brunelli, R. De Angelis, P. Hofman, K. Hartemink, R. Horsleben, E. Ruffine, C. Dickhoff, E. Prisciandaro, J. Derks, I. Bahce, A. Mariolo, E. Xenophontos, N. Giaj Levra, I. Houda, M. Brandao, T. Berghmans
Journal: Journal of Thoracic Oncology (2023)
MA16.03 Tremelimumab plus Durvalumab Prior to Chemoradiotherapy in Unresectable Locally Advanced NSCLC, the Induction Trial
Authors: M.M. Smeenk, J.N.A. van Diessen, T.N. Boellaard, K.J. Hartemink, J.F. de Vries, S.K. Badrising, M. Wondergem, R. Wittenberg, K. Monkhorst, M.M. van den Heuvel, W.S.M.E. Theelen
Journal: Journal of Thoracic Oncology (2023)
EP16.01-04 Standardized Screening of Thoracic Oncology Patients for Clinical Trial Eligibility Increases Enrollment
Authors: M.A. Cislo, M. Mcmillan, N. Shaverdian, C. Simone, D. Gelblum, A. Khan, A. Rimner, A. Burleigh, K. Navarro, D. Spielsinger, D. Gomez
Journal: Journal of Thoracic Oncology (2023)
Third-generation lentiviral gene therapy rescues function in a mouse model of Usher 1B
Authors: Juliane W. Schott, Peixin Huang, Michael Morgan, Jennifer Nelson-Brantley, Ally Koehler, Bryan Renslo, Hildegard Büning, Athanasia Warnecke, Axel Schambach, Hinrich Staecker
Journal: Molecular Therapy (2023)

Usher syndrome 1B (USH1B) is a devastating genetic disorder with congenital deafness, loss of balance, and blindness caused by mutations in the myosin-VIIa (MYO7A) gene, for which there is currently no cure. We developed a gene therapy approach addressing the vestibulo-cochlear deficits of USH1B using a third-generation, high-capacity lentiviral vector system capable of delivering the large 6,645-bp MYO7A cDNA. Lentivirally delivered MYO7A and co-encoded dTomato were successfully expressed in the cochlear cell line HEI-OC1. In normal-hearing mice, both cochlea and the vestibular organ were efficiently transduced, and ectopic MYO7A overexpression did not show any adverse effects. In Shaker-1 mice, an USH1B disease model based on Myo7a mutation, cochlear and vestibular hair cells, the main inner ear cell types affected in USH1B, were successfully transduced. In homozygous mutant mice, delivery of MYO7A at postnatal day 16 resulted in a trend for partial recovery of auditory function and in strongly reduced balance deficits. Heterozygous mutant mice were found to develop severe hearing loss at 6 months of age without balance deficits, and lentiviral MYO7A gene therapy completely rescued hearing to wild-type hearing thresholds. In summary, this study demonstrates improved hearing and balance function through lentiviral gene therapy in the inner ear. Usher syndrome 1B (USH1B) is a devastating genetic disorder with congenital deafness, loss of balance, and blindness caused by mutations in the myosin-VIIa (MYO7A) gene, for which there is currently no cure. We developed a gene therapy approach addressing the vestibulo-cochlear deficits of USH1B using a third-generation, high-capacity lentiviral vector system capable of delivering the large 6,645-bp MYO7A cDNA. Lentivirally delivered MYO7A and co-encoded dTomato were successfully expressed in the cochlear cell line HEI-OC1. In normal-hearing mice, both cochlea and the vestibular organ were efficiently transduced, and ectopic MYO7A overexpression did not show any adverse effects. In Shaker-1 mice, an USH1B disease model based on Myo7a mutation, cochlear and vestibular hair cells, the main inner ear cell types affected in USH1B, were successfully transduced. In homozygous mutant mice, delivery of MYO7A at postnatal day 16 resulted in a trend for partial recovery of auditory function and in strongly reduced balance deficits. Heterozygous mutant mice were found to develop severe hearing loss at 6 months of age without balance deficits, and lentiviral MYO7A gene therapy completely rescued hearing to wild-type hearing thresholds. In summary, this study demonstrates improved hearing and balance function through lentiviral gene therapy in the inner ear.
EP15.03-03 Assessment of the Multidisciplinary Onco-thoracic Consultation Meeting of the University Hospital Center of Tangier
Authors: None Y. Sbaiti, N. Ghozali, M. Meliani, None K. Darif, S. Sarge, M. Amzerin, F.Z. EL M'rabet
Journal: Journal of Thoracic Oncology (2023)
MA13.09 Efficacy and Safety of Poziotinib in HER2 Exon 20 Insertion NSCLC Patients who Received at Least 2 Previous Systemic Therapies
Authors: X. Le, A. Prelaj, C. Baik, N. Tchekmedyian, S. Leu, G. Bhat, J.V. Heymach, R. Cornelissen
Journal: Journal of Thoracic Oncology (2023)
EP13.01-07 Immunohistochemical Classification of Patients with Small Cell Lung Cancer - A Single Center Study
Authors: C.-L. Chiang, Y.-C. Yeh, H.-C. Huang, Y.-H. Luo, C.-I.S. Shen, H.-S. Chao, T.-Y. Chou, D.S. Schrump, Y.-M. Chen
Journal: Journal of Thoracic Oncology (2023)
MA13.08 Beamion Lung 1, a Phase Ia/Ib Trial of the HER2 TKI, BI 1810631 in Patients with Advanced Solid Tumors with HER2 Aberrations
Authors: N. Yamamoto, F. Opdam, M. Barve, H.-Y. Tu, Y.-L. Wu, L. Schroeter, B. Sadrolhefazi, J. Serra, K. Yoh, J. Heymach
Journal: Journal of Thoracic Oncology (2023)
EP13.06-04 Radiotheranostics targeting Delta-Like Ligand 3 Expressing Small-Cell Lung Cancers
Authors: S. Tendler, T. Hoang, D. Bauer, J. Korsen, L. Carter, A. Michel, R. Degregorio, N. Pillarsetty, J.T. Poirier, J.S. Lewis, C.M. Rudin
Journal: Journal of Thoracic Oncology (2023)
MA15.04 Timing of Pre-Biopsy COVID-mRNA Vaccination and PD-L1 Expression in Advanced Non-Small Cell Lung Cancer
Authors: A. Grippin, B. De, K. Fink, D. Swanson, C. Young, E. Chang, A. Johns, E. Cha, X. Wei, S. Dudzinski, J. Lewis, W. Rinsurongkawong, V. Rinsurongkawong, J. Lee, J. Zhang, D.L. Gibbons, A.A. Vaporciyan, J.V. Heymach, S.H. Lin
Journal: Journal of Thoracic Oncology (2023)
OA12.03 An Analysis of the Rate of Second Primary Lung Cancer from CALGB (Alliance) 140503 Trial of Lobar versus Sub-Lobar Resection for T1aN0 NSCLC
Authors: T.E. Stinchcombe, X. Wang, B. Damman, J. Mentlick, R. Landreneau, D. Wigle, D.R. Jones, M. Conti, A.S. Ashrafi, M. Liberman, M. de Perrot, J.D. Mitchell, R. Keenan, T. Bauer, D. Miller, N.K. Altorki
Journal: Journal of Thoracic Oncology (2023)
EP13.03-03 RWD of Atezolizumab Plus Chemotherapy in First Line SCLC
Authors: P. Cruz, L. Fernandez Franco, B. Riesco Montes, S. Falagan, L.E. Chara, S. Simon Alonso, S. Cerezo, L. Gutierrez-Sainz, O. Higuera, J. Villamayor, R. Galan Moral, J.C. Villa, R. Alvarez Cabellos, A.K. Santos Rodriguez, R. Lopez Bajo, M. Serrano, J. Portela, J.R. Muñoz-Rodriguez
Journal: Journal of Thoracic Oncology (2023)
P1.01-07 Asbestos Exposure and Small Cell Lung Cancer. Systematic Review and Meta-Analysis
Authors: J. Rey Brandariz, A. Ruano-Ravina, T. Curiel-García, L. Varela-Lema, C. Candal Pedreira, N. Mourino, M. Pérez Ríos
Journal: Journal of Thoracic Oncology (2023)
OA18.04 Tumor-Derived Complement C3 as a Therapeutic Target in STK11 Mutant Non-Small Cell Lung Cancer
Authors: E. Yau, S. Suzuki, B. Kandar, C. Ting, T. Giridharan, A. Stokolosa, A.N. Khan, B. Segal
Journal: Journal of Thoracic Oncology (2023)
Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Authors: Anni M Y Zhang, Yi Han Xia, Jeffrey S H Lin, Ken H Chu, Wei Chuan K Wang, Titine J J Ruiter, Jenny C C Yang, Nan Chen, Justin Chhuor, Shilpa Patil, Haoning Howard Cen, Elizabeth J Rideout, Vincent R Richard, David F Schaeffer, Rene P Zahedi, Christoph H Borchers, James D Johnson, Janel L Kopp
Journal: Cell Metabolism (2023)
EP13.03-14 A Comparative Analysis between Real-World Data and Clinical Trials to Evaluate Differences in Outcomes for SCLC Patients
Authors: L. Marzano, A. Dan, S. Tendler, A.S. Darwich, J. Raghothama, L. De Petris, R. Lewensohn, S. Meijer
Journal: Journal of Thoracic Oncology (2023)
EP14.01-01 Does Delaying Surgery Following Induction Chemotherapy Compromise Survival in Patients with Malignant Pleural Mesothelioma?
Authors: L.-Y. Wong, I. Baiu, M. Leipzig, A. Titan, D. Liou, N. Lui, M.F. Berry, J. Shrager, L. Backhus
Journal: Journal of Thoracic Oncology (2023)
EP12.03-06 A Retrospective Analysis on the Lung Cancer Specimens for Multi-CDx System in Keio University Hospital
Authors: A. Saito, H. Terai, T.-J. Kim, K. Emoto, R. Kawano, K. Nakamura, H. Hayashi, H. Takaoka, A. Ogata, K. Kinoshita, F. Ito, L. Shigematsu, M. Okada, T. Fukushima, A. Mitsuishi, T. Shinozaki, K. Ohgino, S. Ikemura, H. Yasuda, I. Kawada, K. Soejima, H. Nishihara, K. Fukunaga
Journal: Journal of Thoracic Oncology (2023)
OA10.06 Recognizing Early Adopters of Non Stigmatizing Language at IASLC WCLC 2022
Authors: C. Lockstadt, J. Feldman, J.L. Studts, J.S. Ostroff, L. Liu, M.M. Pasquinelli, L.E. Feldman
Journal: Journal of Thoracic Oncology (2023)
MA19.06 Artificial Intelligence as Concurrent Reader in Prospective European Lung Cancer Screening (4-IN-THE-LUNG-RUN) Trial
Authors: M. Vonder, C. van der Aalst, J. Hubert, D. Moldovanu, A. Schmitz, S. Delorme, J.W. Gratama, M. Silva, H. de Koning, M. Oudkerk
Journal: Journal of Thoracic Oncology (2023)
EP06.03-14 Genomic Alterations in Advanced Lung Cancer Patients Compared via CGP and Hotspot Panel Test in a Bangladeshi Tertiary Hospital
Authors: Q. Chowdhury, M.A. Rahman, F.A. Begum, M.M. Hasan, M. Khair, A.K.M.A. Haque, M.A. Hossain
Journal: Journal of Thoracic Oncology (2023)
EP06.03-03 Oncogenic Drivers of Pulmonary Invasive Mucinous Adenocarcinoma, Detected by Trusight Oncology 500
Authors: K. Shinada, Y. Hiroshima, S. Murakami, A. Narita, S. Katakura, T. Kondo, T. Kato, H. Ito, T. Yokose, H. Saito
Journal: Journal of Thoracic Oncology (2023)
OA14.03 Six-year Survival and HRQoL Outcomes with 1L Nivolumab + Ipilimumab in Patients with Metastatic NSCLC from CheckMate227
Authors: S.S. Ramalingam, T.-E. Ciuleanu, R. Bernabe Caro, M. Nishio, H. Mizutani, J.-S. Lee, C. Audigier-Valette, R. Sangha, L. Urban, J.A. Burgers, A. Pluzanski, K.H. Lee, B. Zurawski, M. Schenker, S. Peters, L.G. Paz-Ares, H. Borghaei, K.J. O’Byrne, J.R. Brahmer, R.G. Gupta, J. Bushong, L. Li, Y. Yuan, S.I. Blum, M. Reck
Journal: Journal of Thoracic Oncology (2023)
MA11.05 Identification of Bio-Immune Markers that Differentiate Long-Term Survivors from Relapse in Patients with Early-Stage Lung Adenocarcinomas
Authors: Y. Lou, Y. Liu, J. Kachergus, Y. Ma, A. Khoor, M. Thomas, I. Makey, Y. Asmann, X. Wang, K. Knutson, A. Thompson
Journal: Journal of Thoracic Oncology (2023)
Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial
Authors: Fei Ma, Min Yan, Wei Li, Quchang Ouyang, Zhongsheng Tong, Yuee Teng, Yongsheng Wang, Shusen Wang, Cuizhi Geng, Ting Luo, Jincai Zhong, Qingyuan Zhang, Qiang Liu, Xiaohua Zeng, Tao Sun, Qinguo Mo, Hu Liu, Ying Cheng, Jing Cheng, Xiaojia Wang, Jianyun Nie, Jin Yang, Xinhong Wu, Xinshuai Wang, Huiping Li, Changsheng Ye, Fangli Dong, Shuchao Wu, Xiaoyu Zhu, Binghe Xu
Journal: BMJ (2023)

Abstract Objective To assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive metastatic breast cancer. Design Randomised, double blind, placebo controlled, multicentre, phase 3 trial. Setting 40 centres in China between 6 May 2019 and 17 January 2022. Participants 590 female patients (median age 52 (interquartile range 46-58) years) with untreated HER2 positive metastatic breast cancer. Interventions Eligible patients were randomised 1:1 to receive either oral pyrotinib (400 mg once daily) or placebo, both combined with intravenous trastuzumab (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m 2 ) on day 1 of each 21 day cycle. Randomisation was stratified by treatment history of trastuzumab in the (neo)adjuvant setting and hormone receptor status. Patients, investigators, and the sponsor’s study team were masked to treatment assignment. Main outcome measures The primary endpoint was progression-free survival as assessed by the investigator. Results Of the 590 randomised patients, 297 received pyrotinib, trastuzumab, and docetaxel treatment (pyrotinib group), and 293 received placebo, trastuzumab, and docetaxel treatment (placebo group). At data cut-off on 25 May 2022, the median follow-up was 15.5 months. The median progression-free survival according to the investigator was significantly longer in the pyrotinib group than in the placebo group (24.3 (95% confidence interval 19.1 to 33.0) months versus 10.4 (9.3 to 12.3) months; hazard ratio 0.41 (95% confidence interval 0.32 to 0.53); one sided P&lt;0.001). Treatment related adverse events of grade 3 or higher were reported in 267 (90%) of the 297 patients in the pyrotinib group and 224 (76%) of the 293 patients in the placebo group. No treatment related deaths occurred in the pyrotinib group, and one (&lt;1%; diabetic hyperosmolar coma) treatment related death occurred in the placebo group. Survival and toxicities are still under assessment with longer follow-up. Conclusions Pyrotinib, trastuzumab, and docetaxel showed superiority by significantly improving progression-free survival compared with placebo, trastuzumab, and docetaxel in patients with untreated HER2 positive metastatic breast cancer. The toxicity was manageable. The findings support this dual anti-HER2 regimen as an alternative first line treatment option in this patient population. Trial registration ClinicalTrials.gov NCT03863223 .
EP13.05-01 Early ctDNA Changes and Clinical Outcomes in Extensive Stage Small Cell Lung Cancer Patients on Nivolumab and Temozolomide
Authors: J.S. Gheeya, L. Wei, L. Bucheit, C. Pilcher, V. Sukrithan, B. Konda, S. Ferguson, M. Jukich, H. Savardekar, E. Schwarz, R. Norman, R. Wesolowski, W. Carson, J. Kaufman, A. Alahmadi, R. Memmott, P. Shields, K. He, E. Bertino, C. Presley, D.P. Carbone, C. Verschraegen, G.A. Otterson, D. Owen
Journal: Journal of Thoracic Oncology (2023)
EP17.04-06 Clinical Outcomes and Lack of Health Equity in Minority Patients with Unresectable Non-small Cell Lung Cancer (NSCLC) Treated with Durvalumab
Authors: A. Fares, N. Theik, K. Dumais, D. Walker, M. Rodriguez, F. Dickson, G. Swaby, A.M. Alvarez, L.E. Raez
Journal: Journal of Thoracic Oncology (2023)
EP14.03-06 PULS - An International Collaboration for Collection and Assessment of Data from Patients with PUL Monary Artery Sarcoma
Authors: O. Lauk, M.B. Kirschner, U. Held, N. Bosbach, T. Verbelen, M. de Perrot, B. Yildizeli, B. Sepesi, N. Deboever, B. Moser, S. Blackmon, I. Opitz
Journal: Journal of Thoracic Oncology (2023)